The proposal that David Mach is submitting will help define the origin of bone cancer pain and begin to dissect out mechanism that are involved in the generation and maintenance of this pain. The experiments that David presented in the Research Training Proposal employ cutting-edge technologies and will position David to be a leader in the field of cancer pain research. A critical feature of David's past and future success has been his ability to closely interact with both basic and clinical scientists and to focus on issues in basic science that will have a direct impact on patient care. Thus, using the first animal model of bone cancer pain that he was involved in generating David will be examining sensory and sympathetic innervation of bone as tumor growth and bone remodeling occur. He will study the extent to which the C-fiber sensory innervation or sympathetic innervation of bone is involved in the regulation of tumor growth, tumor angiogenesis, osteoclast proliferation, and bone destruction/remodeling. David will define the cellular and neurochemical changes that occur in the spinal cord, dorsal column nuclei, dorsal ganglia, and sympathetic ganglia as the bone is destroyed/remodeling. David will define the cellular and neurochemical changes that occur in the spinal cord, dorsal column nuclei, dorsal root ganglia, and sympathetic ganglia as the bone is destroyed/remodeled. These studies should provide David with both the training and the publications so that at the end of his fellowship he will be recognized as a highly productive and innovative clinical-scientist. [unreadable] [unreadable]